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An 84-year-old woman receiving warfarin for antiphospholipid antibody syndrome and who had a history of bilateral lower extremity amputations presented to the emergency department with severe bilateral necrotic changes over her legs and arms (Figures 1 and 2). She had begun warfarin therapy 3 months earlier for newly diagnosed antiphospholipid antibody syndrome. Her International normalized ratio (INR), which had been 6.04 six days prior to admission, was 3.63 on admission. Skin biopsy specimens revealed necrosis secondary to vascular thrombosis. A warfarin-induced etiology was suspected, and the drug was discontinued.
Unlike warfarin-induced skin necrosis, which classically presents centrally over adipose tissue approximately 3 days after starting warfarin in the setting of congenital protein C deficiency,
which is normally balanced by warfarin's ability to prevent thrombin formation by depleting other procoagulant factors. However, in patients with warfarin-induced venous limb gangrene, warfarin does not adequately prevent thrombin-antithrombin complex formation.
This patient's hypercoagulability from her antiphospholipid antibody syndrome, abrupt depletion of protein C as reflected by her elevated INR, and failure of warfarin to prevent thrombin-antithrombin formation, likely led to formation of multiple microthrombi in the distal extremities. It is unclear why this phenomenon occurs in some patients but not others.
The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.